Smooth film laminated elastomer articles

ABSTRACT

A method for manufacturing at least one elastomeric article is provided. The method includes placing into a mold an assembly of an uncured elastomeric sheet, a first film fully covering the elastomeric sheet and a second film covering the first film, such that the second film is in contact with and positioned between the first film and an interior surface of the mold. The method further includes curing the assembly in the mold, such that the first film is laminated onto the elastomeric sheet thereby forming the at least one elastomeric article.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/599,259, titled “Smooth Film Laminated Elastomeric Articles,”filed on Dec. 15, 2017, the entire contents of which are incorporatedherein by reference.

BACKGROUND OF THE DISCLOSURE

The present invention is generally related to elastomeric articles, andmore particularly, to elastomeric stoppers and pistons.

To protect sensitive drug products from extractable and leachablesubstances originating from a container for the drug product, whichincludes an elastomer seal or other closure, e.g., stopper or piston, itis known to include a film laminate on the elastomer seal or closure onthe drug contact surface (i.e., in between the drug and the elastomer)to improve product performance, and is an important risk mitigationstrategy to avoid or reduce unwanted extractables and leachables fromthe elastomer. For example, many conventional plastic or glass syringeassemblies have either a coated or uncoated elastomeric piston. Forcoated pistons, the distal surface, typically referred to as the drugcontact surface, is usually coated with an inert film in order to reducedrug interactions with the elastomeric material of the piston. Theentire surface of the piston, and more particular the peripheral tubularsurface, however, is usually not coated. That is, the cylindricalsidewalls, including sealing ribs, of conventional elastomer pistons areleft with bare elastomer, in order to provide adequate sealing. This isalso typically the case for coated vial stoppers. That is, the drugcontact surface is coated with an inert film, but the bottom of theflange and external sidewalls that contact the vial remain uncoated toprovide better sealing effect. As used herein, the sealing surfacerefers to the circumferential sidewall of a piston or stopper with orwithout sealing ribs.

One consequence of having bare elastomer in contact with the glassbarrel is that frictional forces prevent smooth and easy operation ofthe syringe. As a result, conventionally, the syringe barrel is treatedwith silicone oil or silicone is “baked-on” it to reduce the staticfrictional force, which is referred to as the break-loose force, and toreduce the dynamic frictional force, which is referred to as the glideor extrusion force.

However, silicone oil has been known to interact with some biologicaldrugs. Silicone oil has also been known to separate from the barrel andbecome injected into a patient with the drug. Moreover, regulatoryguidance typically teaches away from using silicone oil in ophthalmicapplications, because lasers are often used for surgery in and aroundthe eye and silicone oil has been known to outgas under hightemperatures which occur during laser surgery.

What is desired, therefore, is an elastomer which does not interact withthe drug or which produces the fewest extractables and leachables. Whatis also desired is a container system that is not a source of siliconeoil.

Another drawback associated with manufacturing both partial filmlaminated stoppers and pistons is that additional manufacturing stepsare required, as compared to manufacturing processes for producingunlaminated or fully laminated stoppers and pistons. That is, theelastomeric article undergoes a so-called “two-step” process, in whichthe piston tip (distal end) or stopper bottom, the ends in contact withthe drug product, are first partially cured with the film separatelyfrom the respective piston base or stopper flange, and then the pistontip and piston base or stopper bottom and stopper flange are combinedand then fully cured in a subsequent step.

However, conventional stoppers and pistons typically do not include afilm laminated over their entire external surface. This is because evenminute imperfections in the laminated film layer would enablepercolation of gasses or fluids past the seal between the laminated filmlayer and the container (i.e., a syringe, cartridge or vial) which maycompromise the container closure integrity (CCI). In particular,scratches or small defects which result in a continuous path across thesealing surface, i.e., the interface between the film-side of anelastomer laminated with an inert film and the container (syringe,cartridge or vial) which prevents the drug from escaping to the outsideof the container, can severely compromise CCI. For example, on a pistonused in a syringe, an axial scratch, perpendicular to the sealing riband parallel to the longitudinal axis of the syringe would create a pathcompromising CCI (see FIG. 4A). Scratches around the circumference ofthe piston, parallel to the sealing rib, may also compromise CCI(although such scratches may not necessarily cause CCI failure, such asdrug leakage) (FIG. 4B). Also, a sufficiently high overall surfaceroughness (Ra) typically will still allow percolation of drug product orgas through a random path of roughness, and therefore compromise CCI.

In systems which use silicone, the silicone itself has been shown toreduce CCI issues. However, in silicone-free drug-containment systems,no silicone is present to reduce CCI issues.

Therefore, it would be desirable to provide a silicone-freedrug-containment system, in which the closure (i.e., piston or stopper)is entirely film laminated, and in which the CCI at the interface of thesealing surface of the closure and container substrate is maintained ata sufficiently high level. Another benefit of having the entire or alarge portion of piston or stopper coated with an inert film, is toprotect the elastomer from unintended exposure to chemicals includingsolvents used in the manufacturing process, such as dimethyl sulfoxide(DMSO). DMSO has been known to cause rubber to swell, which may causesome dimensions of a stopper or piston to increase beyond suitabletolerances.

Therefore, what is also desired is a piston or stopper having adequatesealing properties which is entirely film-laminated, so that it may bemade using a single curing process or step. In addition, it would bedesirable to provide film laminated pistons or stoppers configured to beused in a silicone-free glass syringe and having similar sealing andfrictional properties as a conventional piston made with the two-stepprocess and coated with silicone oil, or using a syringe or cartridgebarrel coated with silicone oil or having based on silicone.

BRIEF SUMMARY OF THE DISCLOSURE

One embodiment of the present invention is related to a method formanufacturing at least one elastomeric article comprising the steps of:placing into a mold an assembly of an uncured elastomeric sheet, a firstfilm fully covering the elastomeric sheet and a second film covering thefirst film, such that the second film is in contact with and positionedbetween the first film and an interior surface of the mold; and curingthe assembly in the mold, such that the first film is laminated onto theelastomeric sheet thereby forming the at least one elastomeric article.

Another embodiment of the present invention is directed to anelastomeric article for sealing a container comprising an elastomericbody having an external sidewall surface and an external crown surface,and a first fluoropolymer film layer having an internal surface and anexternal surface. The internal surface of the first fluoropolymer filmlayer is laminated to an entirety of the external sidewall and crownsurfaces of the elastomeric body. The external crown surface of thefirst fluoropolymer film layer includes a drug contact surfaceconfigured to contact a drug contained in the container, and theexternal sidewall surface includes a sealing surface configured tocontact an interior surface of the container.

Another embodiment of the present invention relates to a device forinjecting a drug. The device comprises a silicone-free barrel and anelastomeric piston having a laminated film layer in contact with thesilicone-free barrel. An interface between the laminated film layer andthe silicone-free barrel having a seal which withstands leakage of gasof less than about 6×10⁻⁶ atm*cc/sec.

Another embodiment of the present invention relates to a method formanufacturing an elastomeric article comprising the steps of: placing anuncured elastomeric sheet and a first film fully the elastomeric sheetinto a mold; curing the elastomeric sheet with the first film in themold into at least one elastomeric article; removing the elastomericarticles from the mold; and removing the first film from the at leastone elastomeric article.

BRIEF DESCRIPTION OF THE DRAWINGS

The following detailed description of aspects of the disclosure will bebetter understood when read in conjunction with the appended drawings.It should be understood, however, that the invention is not limited tothe precise arrangements and instrumentalities shown. In the drawings:

FIG. 1 depicts a one-step method of manufacturing an elastomeric articlein accordance with an embodiment of the present invention;

FIG. 2 depicts the first step of a two-step method of manufacturing anelastomeric article in accordance with an embodiment of the presentinvention;

FIG. 3 depicts the second step of the two-step method of manufacturingan elastomeric article in accordance with an embodiment of the presentinvention;

FIG. 4A shows a prior art piston having axial scratches perpendicular tothe sealing rib and parallel to the axis of rotational symmetry whichcreate a path compromising CCI;

FIG. 4B shows a prior art piston having scratches around thecircumference of the piston parallel to the sealing rib, which maycompromise CCI;

FIGS. 5A and 5C are scanning electron microscope (SEM) images (150×magnification) of the drug contact surface of an elastomeric pistonproduced by a method in accordance with an embodiment of the presentinvention;

FIGS. 5B and 5D are SEM images (150× magnification) of thecircumferential side surface, and more particularly a sealing rib, of anelastomeric piston produced by a method in accordance with an embodimentof the present invention;

FIGS. 6A and 6C are SEM images (150× magnification) of the drug contactsurface of an elastomeric piston produced by a method which did notutilize a release film layer;

FIGS. 6B and 6D are SEM images (150× magnification) of thecircumferential side surface, and more particularly a sealing rib, of anelastomeric piston produced by a method which did not utilize a releasefilm layer;

FIG. 7 is a graphical plot of various area roughness parameters ofsamples of elastomeric articles manufactured by a method in accordancewith an embodiment of the present invention and comparative articles;

FIG. 8 is a graphical plot of various area roughness parameters ofsamples of elastomeric articles manufactured by a method in accordancewith an embodiment of the present invention and comparative articles,with application of a 2 μm Gaussian filter;

FIG. 9 is a graphical plot of various area roughness parameters ofsamples of elastomeric articles manufactured by a method in accordancewith an embodiment of the present invention and comparative articles,with application of a 0.08 μm Gaussian filter;

FIG. 10 is a graphical plot of various profile roughness parameters ofsamples of elastomeric articles manufactured by a method in accordancewith an embodiment of the present invention and comparative articles;

FIG. 11 graphically depicts single contact profilometry measurements tohighlight the surface roughness difference between elastomeric articlesproduced according to the claimed invention and a conventionalelastomeric article;

FIG. 12 graphically depicts the measurements of FIG. 11;

FIG. 13 shows optical microscopy images of an elastomeric pistonaccording to the present invention, which has an improved surfacefinish, as compared to those prepared by a conventional process notinvolving a release film layer;

FIG. 14 illustrates CCI in a cyclic olefin polymer container, and moreparticularly a container formed of a polymer made and/or sold under thetrademark Crystal Zenith® and sourced from Daikyo Seiko, Ltd.(hereinafter referred to as “Crystal Zenith® polymer), for InventiveSample C and Comparative Sample 4 using helium leak testing;

FIG. 15 illustrates CCI in Crystal Zenith® polymer, Silicone-Free Glass,and Baked-On Silicone Glass for Inventive Sample C using helium leaktesting;

FIG. 16 illustrates CCI in Siliconized Glass and Baked-On Silicone Glassfor Inventive Sample D and Comparative Sample 5 using helium leaktesting;

FIGS. 17 and 18 illustrate the force performance of Inventive Sample C.

FIG. 19A depicts an enhanced optical image of the surface of ComparativeSample 1;

FIG. 19B depicts the waviness and roughness profiles of the surface ofComparative Sample 1;

FIG. 20A depicts an enhanced optical image (intensity used to show depthand height) of the surface of Comparative Sample 2;

FIG. 20B depicts the waviness and roughness profiles of the surface ofComparative Sample 2;

FIG. 21A depicts an enhanced optical image of the surface of ComparativeSample 3;

FIG. 21B depicts the waviness and roughness profiles of the surface ofComparative Sample 3;

FIG. 22A depicts an enhanced optical image of the surface of InventiveSample 1;

FIG. 22B depicts the waviness and roughness profiles of the surface ofInventive Sample 1;

FIG. 23A depicts an enhanced optical image of the surface of InventiveSample 2; and

FIG. 23B depicts the waviness and roughness profiles of the surface ofInventive Sample 2.

DETAILED DESCRIPTION OF THE DISCLOSURE

Referring to FIG. 1, there is shown a method of manufacturing anelastomeric article, such as a piston 11, using a first mold 14, anelastomer sheet 44, a first film 16 and more particularly an inert filmlayer or barrier layer 16, and a second film 46 and more particularly arelease film layer 46 in a one-step molding process, and moreparticularly in a one-step compression molding process. The first mold14 includes an upper mold half 15 having a protrusion 15 a and a lowermold half 17 having an open cavity 17 a. The open cavity 17 a ispreferably an open heated mold cavity. In a preferred embodiment, thefirst mold 14 includes a plurality of upper and lower mold halves 15, 17arranged in an array.

The elastomer sheet 44 is preferably formed of one or more elastomericmaterials in a partially cured stage. In a preferred embodiment, theelastomeric material is either a thermoset elastomer or a thermoplasticelastomer (TPE). The elastomeric material used for the elastomericclosure can be, for example, a synthetic or natural rubber, such asbutyl rubber, isoprene rubber, butadiene rubber, halogenated butylrubber (e.g., bromobutyl rubber), ethylene propylene terpolymer,silicone rubber, combinations thereof and the like. Preferably, theelastomeric material is a butyl or halobutyl elastomer.

The inert film layer 16 is preferably formed of a polymer, and moreparticularly a highly inert polymer with good barrier properties andlubricity. The film 16 preferably is an olefin polymer and could includea cyclic olefin polymer. More preferably, the inert film layer 16 isformed of a fluoropolymer, such as tetrafluoroethylene or ethylenetetrafluoroethylene. Some non-limiting examples of polymers that may beused to form the inert film layer 16 include tetrafluoroethylene,polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE),fluorinated ethylene propylene (FEP), polyvinylidene fluoride (PVF),polyvinylidene difluoride (PVDF), polychlorotrifluoroethylene (PCTFE),perfluoroalkoxy alkanes (PFA), ethylene chlorotrifluoroethylene (ECTFE),perfluoroelastomer (FFPM), fluoroelastomer polymer (FPM), polyethylene(PE), cyclic olefin polymer (COP), cyclic olefin copolymer (COC) andpolypropylene (PP). The inert film layer 16 preferably has a thicknessof from 0.5 μm to 300 μm, more preferably from 10 μm to 150 μm, and mostpreferably from 25 μm to 100 μm.

An even wider array of polymers are suitable for use in forming therelease film layer 46, because the chemical requirements are different.That is, all of the above exemplary polymers identified for the materialof the inert film layer 16 may also be used to form the release filmlayer 46. In addition, high temperature-compatible polymers, such aspolyimides or silicones, are also suitable for use in forming therelease film layer 46. Similar to the inert film layer 16, the releasefilm layer 46 preferably has a thickness of from 0.5 μm 1 to 300 μm,more preferably from 10 μm to 150 μm, and most preferably from 25 μm to100 μm.

The elastomer sheet 44 has a first surface 44 a and an opposing secondsurface 44 b. The inert film layer 16 has a first surface 16 a and anopposing second surface 16 b. The release film layer 46 has a firstsurface 46 a and an opposing second surface 46 b. The first surface 16 aof the inert film layer 16 may be surface modified/treated to have alower water contact angle and higher surface energy than unmodifiedsecond surface 16 b. Preferably, the first surface 16 a of the inertfilm layer 16 is etched, and more preferably plasma etched. Surfacemodification/treatment of the first surface 16 a of the inert film layer16 may permit it to bond to the elastomer sheet 44 strongly aftercompression molding. Because the second surface 16 b of the inert filmlayer 16 is unmodified, it has a higher water contact angle and lowersurface energy, which allows it to be more easily detached from anuntreated side of another film, such as release film layer 46

The elastomer sheet 44, inert film layer 16, and release film layer 46may be firmly joined with each other or independent from one another, inthis order, and placed loosely on top of each other when introduced intothe first mold 14. More particularly, for placement in the mold 14, therelease film layer 46 is arranged such that the second surface 46 b willcontact the interior surface 19 of an open cavity 17 a of the lower moldhalf 17; the inert film layer 16 is arranged such that the secondsurface 16 b of the inert film layer 16 is in contact with the firstsurface 46 a of the release film layer 46, and more preferably entirelycovered by the first surface 46 a of the release film layer 46; and theelastomer sheet 44 is arranged such that the first surface 44 a isarranged so as to contact a protrusion 15 a of the upper mold half 15and the second surface 44 b of the elastomer sheet 44 is in contact withthe first surface 16 a of the inert film layer 16, and more preferablythe entirety of the second surface 44 b of the elastomer sheet 44 iscovered by the first surface 16 a of the inert film layer 16. The twomold halves 15, 17 are then brought into contact with each other, suchthat each protrusion 15 a contacts the first surface 44 a of theelastomer sheet 44 and forces the layered arrangement of the elastomersheet 44, inert film layer 16 and release film layer 46 into the opencavity 17 a, so as to compress and mold the arrangement of the elastomersheet 44, inert film layer 16, and release film layer 46 within eachopen cavity 17 a in a single compression molding step.

This compression molding step is carried out at a temperature of 120° C.to 310° C. and a pressure of about 40 to 350 kg/cm² for a duration of afew seconds to 30 minutes. More preferably, the single compressionmolding step is carried out at a temperature of about 120° C. to 220° C.and a pressure of about 40 to 70 kg/cm² for a duration of about 30seconds to 30 minutes. Most preferably, the single compression moldingstep is carried out at a temperature of about 140° C. to 220° C. and apressure of about 40 to 70 kg/cm² for duration of about 2 to 15 minutes.

In a preferred embodiment, the compression molding step is carried outat a temperature of 160° C. to 165° C. and a pressure of 50 kg/cm² for aduration of about 15 minutes.

In another preferred embodiment, the compression molding step is carriedout at a temperature of 160° C. to 175° C. and a pressure of about 40 to70 kg/cm² for a duration of about 8 minutes.

During the compression molding step, the elastomeric sheet 44 isvulcanized under the influence of heat and pressure and isnon-detachably joined with the inert film layer 16. More particularly,the elastomeric sheet 44 forms the body 21 of the piston 11 and theinert film layer 16 becomes a laminated film 23 non-detachably formedover the surface, and more preferably the sidewall and crown surfaces ofthe body 21. This process occurs below the melting temperature of boththe inert film layer 16 and the release film layer 46 so that the filmsdo not fuse together. Thus, the release film layer 46, on the otherhand, becomes detachably joined to the laminated film layer 23. If afilm is not melted, the layers can be separated. Different films can beused for the release layer than the film layer on the elastomericarticle (dissimilar chemistry and/or higher melting points). Forexample, polyamide film is used as a release layer in many composites,which melts above 340° C.

After curing or vulcanization, the piston 11 is removed from the firstmold 14 and the release film layer 46 is then peeled away from thepiston 11. The release film layer 46 does not adhere to the inert filmlayer 16, as such, it can be mechanically separated from the inert filmlayer 16 as a continuous sheet or as cut portions from the individualpistons by, for example, grasping and pulling, blowing with fluid, orpeeling by abrasion, among other techniques.

Prior to curing of the assembly of the elastomeric sheet 44, inert filmlayer 16 and release film layer 46 in the molding process, the inertfilm layer 16 has a surface roughness characterized by a first peakdensity. After the curing process and removal of the release film layer46, the inert film layer 16, and more particularly the laminated filmlayer 23, has a surface roughness characterized by a second peakdensity, and the second peak density is increased relative to the firstpeak density. Preferably, the peak density of the inert film layer 16 isincreased by at least 3%, and more preferably by at least 25%, after thecuring process and removal of the release film layer 46. Moreparticularly, the peak density of the inert film layer 16 is preferablyincreased by 3% to 165%, and more preferably by 25% to 35%, after thecuring process and removal of the release film layer 46.

Although the process is discussed in terms of producing a piston 11, askilled artisan would readily appreciate that the same process could beused for producing other elastomeric articles, such as a stopper orother closures.

Referring to FIGS. 2 and 3, there are shown methods of manufacturing anelastomeric article, such as a piston 12, according to anotherembodiment of the present invention. The process of FIG. 2 utilizes asecond mold 24 that is sized and shaped to form a molded portion of anelastomeric article, as a piston crown 12 a. The mold 24 thus serves asthe initial mold for the manufacturing process. The process of FIG. 3uses the mold 14 (i.e., the mold shown in FIG. 1) that is sized andshaped to form the whole elastomeric article (e.g., the piston 12).FIGS. 2 and 3 together illustrate a two-step molding process, and moreparticularly in a two-step compression molding process, according to anembodiment of the present invention.

Referring to FIG. 2, the mold 24 used for the first step of the two-stepmolding process includes an upper mold half 25 having an open cavity 25a and a lower mold half 27 having an open cavity 27 a. The open cavities25 a, 27 a are preferably open heated mold cavities. In a preferredembodiment, the first-step mold 24 includes a plurality of upper andlower mold halves 25, 27 arranged in an array. As with the one-stepmolding process, the elastomer sheet 44, the inert film layer 16, andthe release film layer 46 may be firmly joined with each other orindependent from one another, in this order, and placed loosely on topof each other when introduced into the second mold 24. The arrangementof the elastomer sheet 44, the inert film layer 16, and the release filmlayer 46 is the same as described above with respect to FIG. 1.

The process conditions for the molding step shown in FIG. 2 are the sameas those discussed above for the one-step process of FIG. 1. As with theone-step process of FIG. 1, the elastomeric sheet 44 is vulcanized underthe influence of heat and pressure and is non-detachably joined with theinert film layer 16, such that the vulcanized elastomeric material formsthe body 31 of the piston crown 12 a and the inert film layer 16 becomesa laminated film layer 33 non-detachably formed on the surface of thepiston crown 12 a (i.e., a laminated piston crown 12 a). The releasefilm layer 46, on the other hand, is detachably joined to the laminatedfilm layer 33.

After vulcanization, the laminated piston crown 12 a is removed from themold 24 with the release film layer 46 intact on the laminated pistoncrown 12 a. Next, the assembly of the laminated piston crown 12 a andthe release film layer 46 is trimmed and placed into the mold 14, asshown in FIG. 3, such that the release film layer 46 is in contact withthe interior surface 19 of an open cavity 17 a of the lower mold half 17and the release film layer 46 is sandwiched between the laminated pistoncrown 12 a and the open cavity 17 a. In the two-step process of FIGS. 2and 3, therefore, the mold 14 is a second-step mold.

Next, a second elastomeric sheet 44 is placed in the first mold 14, andmore particularly over the open cavities 17 a of the lower mold half 17.The two mold halves 15, 17 are then brought into contact with eachother, such that each protrusion 15 a contacts the first surface 44 a ofthe second elastomer sheet 44 and forces the material of the secondelastomer sheet 44 into the open cavity 17 a and into contact with thelaminated piston crown 12 a, so as to compress and mold the arrangementof the second elastomer sheet 44 and the laminated piston crown 12 awithin each open cavity 17 a in compression molding step. Vulcanizationproceeds as described above with respect to FIG. 1, in order to producea piston 12 having a removable release film layer 46 for masking thecrown portion 12 a in subsequent operations (such as an operation toproduce a piston having silicone oil on only the exposed elastomersides, but not on the laminated crown portion 12 a).

Prior to curing of the assembly of the elastomeric sheet 44, inert filmlayer 16 and release film layer 46 in the molding process, the inertfilm layer 16 has a surface roughness characterized by a first peakdensity. After the curing process and removal of the release film layer46, the inert film layer 16, and more particularly the laminated filmlayer 33, has a surface roughness characterized by a second peakdensity. The second peak density is increased relative to the first peakdensity. Preferably, the peak density of the inert film layer 16 isincreased by at least 3%, and more preferably by at least 25%, after thecuring process and removal of the release film layer 46. Moreparticularly, the peak density of the inert film layer 16 is preferablyincreased by 3% to 165%, and more preferably by 25% to 35%, after thecuring process and removal of the release film layer 46.

It will be understood that the first-step mold 24 may alternatively besized and shaped to form a different portion of a different elastomericarticle (e.g., the body of a stopper), instead of a piston crown 12 a,and the second-step mold 14 may be sized and shaped to form a differentelastomeric article instead of a piston.

Molding an elastomeric article, such as a piston or a stopper, in atwo-step process produces an article having a drug interface portioncoated with the inert film 16 and the remaining surface of theelastomeric article being uncovered (i.e., bare elastomer).

The resulting elastomeric article 11, 12 produced by the methods of thepresent invention is a smooth film-laminated elastomeric article. In oneembodiment, the resulting elastomeric article 11, 12 is a silicone-freeelastomeric article. The release film layer 46, which is sandwichedbetween the elastomeric sheet 44 covered with the inert film layer 16and the mold cavity surface 19, protects the smooth film-laminatedarticle (i.e., the piston 11) from damage during the manufacturingprocess, such as damage that might occur to the laminated film 23, 33from sliding past the mold surface 19 during the molding and/ordemolding steps. The release film layer 46 also protects the laminatedfilm 23, 33 from any texture which would have been imparted to it by themold surface 19 (i.e., it is a mechanical analogy to a low pass filter).The use of the release film layer 46 also protects the laminated film23, 33 from any material contamination which might be imparted to it bythe mold surface 19, such as processing aids used in the moldingprocess, adhered elastomer, or any other environmental contamination.The use of the release film layer 46 creates a unique surface morphologyas a result of the intimate surface-to-surface interfacial contact ofthe laminate films 23, 33 and the release film layer 46 and theirsubsequent separation.

Also, use of the release film layer 46 gives the external surface of thelaminated film layer 23, 33 a mirror-like finish. Thus, elastomericarticles made according to the invention have an exterior surface, andmore particularly, an exterior sealing surface, comprised of a laminatedfilm having a mirror-like finish or that substantially-free ofstriations or substantially smooth. FIG. 13 compares the texture of aplunger with a laminated film according to the invention to that of aconventional laminated plunger and shows that a plunger according to theinvention has an exterior surface that is smooth or with a mirror-likesurface (left hand side), as compared to a conventional film laminatedplunger with an exterior surface that is rough, with striations and notmirror-like (right hand side).

Specific embodiments of the invention will now be described in terms ofthe following non-limiting examples and experiments.

Examples 1-4

Examples 1-4 below utilize four elastomeric pistons laminated with PTFE(i.e., a laminated PTFE film layer covering the body of the piston andthus forming the external sidewall and crown surfaces of the piston) andproduced according to the process described above with respect to FIG. 1with a release film layer of ETFE. For comparison purposes, fourelastomeric pistons each having a PTFE barrier layer were producedaccording to the same process, except that a release film layer was notutilized (hereinafter referred to as Comparative Examples 1-4). Thepiston crown (shown in FIGS. 5A and 5C) and the circumferential sealingsurface, and more particularly the primary sealing rib (shown in FIGS.5B and 5D) of Examples 1-4 have an extremely smooth laminated filmsurface with no clear texture, marks, or striations on the surfaces. Incontrast, the laminated film surfaces of the piston crown (shown inFIGS. 6A and 6C) and the circumferential sealing surface, and moreparticularly the primary sealing rib (shown in FIGS. 6B and 6D) of eachof the Comparative Examples 1-4 has significant surface features, in theform of broken circles, slashes and striations of random depth andlength, pitting of random sizes and depth, flat areas, broken shallowtrenches and the like.

Test 1

A 5-mL elastomeric piston having a laminated PTFE barrier layer wasproduced according to the process described above with respect to FIG.1, utilizing a release film layer formed of ETFE having a 2 mil (˜50 μm)thickness (the analysis was performed on different areas of the firstrib (i.e., the rib closest to the drug contact surface) of the piston toshow variation across the surface, and is accordingly referred to inTable 1 as Inventive Samples A and B) (Inv. Samples A and B). Forcomparison purposes, a bare elastomeric piston was produced using thesame process parameters as that used to produce Inv. Samples A and B,but no laminated film layer or release film layer was utilized (referredto in Table 1 as Comparative Sample 1) (Comp. Sample 1); an elastomericpiston provided with a laminated PTFE barrier film was producedaccording to the same process parameters as used to produce Inv. SamplesA and B, except that a release film layer was not utilized (referred toin Table 1 as Comparative Sample 2) (Comp. Sample 2); and a PTFE filmbefore molding was provided (referred to in Table 1 as ComparativeSample 3) (Comp. Sample 3).

The surface texture of each piston and film was measured using a Keyence3D laser scanning confocal microscope. To determine the area roughnessparameters, the measurement results were evaluated using ISO 25178Surface Texture standard in three different manners: first, with nofilter applied, as reflected by Ex. A-1 through A-5; second, with a 2 μmGaussian filter applied to eliminate the high frequency component of themeasurement and separate waviness from roughness, in accordance with JISB 0632:2001 (ISO 11562:1996) and ISO 16610-21:2011, as reflected by Ex.B-1 through B-5; and third, with a 0.08 μm Gaussian filter applied toeliminate the high frequency component of the measurement and separatewaviness from roughness, in accordance with JIS B 0632:2001 (ISO11562:1996) and ISO 16610-21:2011, as reflected by Ex. C-1 through C-5,in order to determine area roughness parameters of each piston and film.The area roughness parameters are summarized in Table 1 and aregraphically plotted in FIGS. 7-9, where the y-axis is parallel to thelongitudinal axis of the piston, such that the drug contact surface ofthe piston is positioned proximate the top of each graph.

Also, the profile roughness parameters of each sample were collectedfrom a Mitutoyo Surftest profilometer using a low-force probe and aresummarized in Table 2 and plotted in FIG. 10, where the y-axis isparallel to the longitudinal axis of the piston, such that the drugcontact surface of the piston is positioned proximate the top of thegraph. Optical images showing the surface topography of each sampletaken from the 3D laser scanning confocal microscope are provided inFIGS. 19A, 20A, 21A, 22A and 23A, and surface topography of each sampleis shown in FIGS. 19B, 20B, 21B, 22B and 23B.

TABLE 1 Sample Filter Sa (μm) Sz (μm) Str Spc (1/mm) Sdr Sku Sal (μm)Spd (1/mm²) Inv. Sample A None 0.262336 4.1297 0.970222 9266.8141.878123 5.158748 0.270005 1,259,318.00 Inv. Sample B None 0.13278712.2927 0.978388 5030.206 1.294387 59.67023 0.266522 1,015,401.00 Comp.Sample 1 None 1.026478 15.1123 0.565495 4409.993 0.578164 5.7645111.72558 420,438.90 Comp. Sample 2 None 0.437393 4.5524 0.57411 792.31740.017666 5.438234 20.7215 500,808.00 Comp. Sample 3 None 0.033312 1.22440.104636 261.1826 0.001726 58.54961 10.21932 978,239.60 Inv. Sample A  2 um 0.082208 1.066229 0.634141 526.3015 0.022638 3.521474 8.831092263,848.80 Inv. Sample B   2 um 0.073382 3.471453 0.56019 357.64220.023383 21.87629 2.06764 206,612.20 Comp. Sample 1   2 um 0.94923212.7187 0.544209 656.7781 0.109784 5.733194 12.88502 55,100.75 Comp.Sample 2   2 um 0.435485 3.973141 0.444705 96.20823 0.005953 5.50367818.76363 30,802.31 Comp. Sample 3   2 um 0.031641 1.039648 0.11446919.44969 0.000249 70.06189 10.11807 100,523.70 Inv. Sample A 0.08 um0.176165 2.247206 0.746072 3599.218 0.50764 4.2981 0.561229 900,924.80Inv. Sample B 0.08 um 0.106901 7.796973 0.948766 1983.697 0.36473241.39421 0.555849 704,039.70 Comp. Sample 1 0.08 um 1.007319 13.589360.562905 2201.081 0.322836 5.61202 12.19855 253,028.80 Comp. Sample 20.08 um 0.43421 4.395502 0.562864 400.5178 0.00996 5.406948 20.68207248,452.10 Comp. Sample 3 0.08 um 0.033189 12.26598 0.134748 125.59130.002295 2699.859 9.075675 671,310.90 Results are at 50X objective.

TABLE 2 Sample Ra (μm) Rz (μm) RSm (μm) Rku Pc/cm Rλa (μm) Inv. Sample A0.195011 1.626049 10.28698 5.18205 986.5094 2.363367 Inv. Sample B0.123327 2.244208 22.96563 26.7377 481.2344 2.973297 Comp. Sample 10.473978 3.134142 39.95096 3.350478 282.9486 13.34772 Comp. Sample 20.113927 0.568438 44.82615 2.058096 262.8811 9.818667 Comp. Sample 30.025882 0.14815 37.9068 2.304411 272.3878 9.535636

Referring to Table 1, the parameters measured and/or calculated includearithmetic mean height (Sa), maximum height (Sz), texture aspect ratio(Str), arithmetic mean peak curvature (Spc), developed interfacial arearatio (Sdr), kurtosis (Sku), auto-correction length (Sal), and peakdensity (Spd). Arithmetic mean height is the average height of theabsolute value with respect to the average height (non-absolute value)along the sampling length. Peak density is the number of peaks per unitarea. For optical measurements, the smallest detectable peak is afunction of the wavelength of the light source. Filtering the data istypically used to remove noise, but it may also be used to effectivelydefine what qualifies as a peak.

As will be understood by one skilled in the art, although botharithmetic mean height and peak density are parameters used tocharacterize surface roughness, these parameters are not necessarilyrelated to or correlated with each other. For example, when anelastomeric article covered by an inert film is molded (without arelease layer), the inert film conforms to the surface of the mold,assumes the surface profile of the mold, and theoretically assumes theroughness of the mold. Thus, the peak density and the arithmetic meanheight of the inert film are directly related to the peak density andarithmetic mean height of the mold. Subsequent surface treatments on theelastomeric article, such as burnishing, may reduce the height of someof the peaks and effectively reduce the arithmetic mean height. However,the peak density would not necessarily change as a result of these latersurface treatments. Thus, arithmetic mean height and peak density cannotbe considered to be parameters that can be correlated with each other.

Referring to Table 2, the parameters measured and/or calculated includearithmetic mean height (Ra), maximum height (Rz), mean width of profileelements (RSm), kurtosis (Rku), peaks per length (Pc/cm), and arithmeticmean wavelength (Rλa). The parameters shown in Table 2 representmeasurements taken along a sampling line, whereas the parameters shownin Table 1 represent measurements taken over an area. The measurementresults show that the inert film of Comp. Sample 2 likely assumed thesurface profile and roughness of the mold during curing orvulcanization. The mean arithmetic heights (Sa) of the inert film ofInv. Samples A and B were noticeably better than that the meanarithmetic height (Sa) of the bare elastomer of Comp. Sample 1. Also, ascan be seen in Table 1, the peak density (Spd) for Inv. Samples A and Bincreased compared to that of the inert film before molding (i.e., Comp.Sample 3). This is because the external surface of the release filmconformed to the interior surface of the mold, while the inert film ofInv. Samples A and B assumed the surface profile and roughness of therelease film. Thus, it is clear that the release film layer can be usedto purposefully manipulate the surface texture of the inert film layeras a result of the release film layer and inert film layer mechanicallyinteracting with each other during the molding process.

Moreover, during the molding process, the inert film layer 16 and therelease film layer 46 are stretched around 400% as they are forced intothe mold. Stretching the release film layer has two effects. First,surface features may proportionally decrease due to Poisson's ratioeffectively reducing the mean arithmetic height, and second, featuresanalogous to micro cracks may form, effectively creating new peaks andvalleys. In addition, removing the release film layer 46 from the inertfilm layer 16 may create additional peaks. For example, localizedcontact areas of adhesion between the inert film layer 16 and therelease film layer 46 may cause the surface of the inert film to stretchat the contact area when the release film layer 46 is peeled away untilthe adhesive bonds are broken. The stretching of the inert film 16leaves residual deformation peaks on its surface.

That is, the inventors have surprisingly found that not only does therelease film layer 46 protect the laminated film 23, 33 from damage, itactually improves the surface texture of the film. More particularly,the surface roughness, characterized by a peak density (with no filterapplied), of the inert film 16 is increased by 3.8% to 28.7% by themolding process of the present invention in forming the laminated film23, 33. The surface roughness, characterized by a peak density (whenapplying a Gaussian filter of 2.0 microns), of the inert film 16 isincreased by from 105.5% to 162.5% by the molding process of the presentinvention in forming the laminated film 23, 33. The surface roughness,characterized by a peak density (when applying a Gaussian filter of 0.08microns), of the inert film 16 is increased by from 4.9% to 34.2% by themolding process of the present invention in forming the laminated film23, 33.

Also, in one embodiment, a sealing surface configured to contact thecontainer or syringe along a mutual perimeter circumscribing theelastomeric article has a surface roughness characterized by a peakdensity greater than 50,000 peaks/mm² when applying a Gaussian filter of2.0 microns or a peak density greater than 300,000 peaks/mm² whenapplying a Gaussian filter of 0.08 microns; preferably the sealingsurface has a surface roughness characterized by a peak density greaterthan 100,000 peaks/mm² when applying a Gaussian filter of 2.0 microns ora peak density greater than 500,000 peaks/mm² when applying a Gaussianfilter of 0.08 microns; more preferably the sealing surface has asurface roughness characterized by a peak density greater than 150,000peaks/mm² when applying a Gaussian filter of 2.0 microns or a peakdensity greater than 600,000 peaks/mm² when applying a Gaussian filterof 0.08 microns; and most preferably the sealing surface has a surfaceroughness characterized by a peak density greater than 200,000 peaks/mm²when applying a Gaussian filter of 2.0 microns or a peak density greaterthan 700,000 peaks/mm² when applying a Gaussian filter of 0.08 microns.

With an extremely low, direction-independent surface roughness,elastomeric articles produced according to the present invention form anoptimal interface with the container or syringe, and therefore yieldimproved CCI. The inventive elastomeric article is applicable for use insilicone-free systems, i.e., where there is no silicone oil to assist inmitigating CCI issues.

Also, graphically, there is a clear difference in the plots of thesurface profile between the inventive elastomeric articles, producedusing a release film layer, and conventional elastomeric articles, asshown in FIG. 11, even though the average numbers presented for pistonfaces in the graph (FIG. 12) do not appear drastically different. Thecurvature to the trace comes from the underlying curvature of theelastomer article. A collection of the quantitative measurements issummarized in FIG. 12.

The difference in surface finish discussed above is clearly visible in aqualitative visual evaluation. Images in FIG. 13 show an elastomericpiston according to the present invention, which has an improved surfacefinish appearing glossy (labeled as “Smooth”), as compared to thoseprepared by a conventional process not involving a release film layerappearing matte (labeled as “Rough”). The improved surface finish isevenly applied across the sidewall and crown surfaces, while theconventionally produced components possess a larger variability intexture across the visibly rough surface.

Test 2

In addition to Inv. Samples A and B and Comp. Samples 1-3, a number of1-mL long elastomeric pistons provided with a laminated PTFE barrierfilm over the external sidewall and crown surfaces were producedaccording to the process described above with respect to FIG. 1,utilizing a release film layer formed of ETFE having a 2 mil (˜50 μm)thickness (various tests were performed using pistons of this type, andare accordingly referred to in FIGS. 14, 15, 17, and 18 as InventiveSample C) (Inv. Sample C); and a number of 1-mL long elastomeric pistonsprovided with a laminated ETFE barrier film over the external sidewalland crown surfaces were produced according to the same processparameters as used to produce Inv. Sample C (referred to in FIG. 16 asInventive Sample D) (Inv. Sample D). For comparison purposes, a numberof 1-mL long elastomeric pistons were produced using the same processparameters as that used to produce Inv. Sample C (i.e., having alaminated PTFE barrier film), but no release film layer was utilized(referred to in FIG. 14 as Comparative Sample 4) (Comp. Sample 4); and anumber of 1-mL long elastomeric pistons were produced using the sameprocess parameters as that used to produce Inv. Sample D (i.e., having alaminated ETFE film), but no release film layer was utilized (referredto in FIG. 16 as Comparative Sample 5) (Comp. Sample 5).

FIG. 14 illustrates CCI in Crystal Zenith® polymer with PTFE laminatedpistons produced with (Inv. Sample C) and without (Comp. Sample 4)release liners using helium leak testing. Similar to FIG. 14, FIG. 15illustrates CCI in Crystal Zenith® polymer, Silicone-Free Glass, andBaked-On Silicone Glass with PTFE laminated pistons produced withrelease liners (Inv. Sample C) using helium leak testing. In addition,FIG. 16 illustrates CCI in Siliconized Glass, and Baked-On SiliconeGlass with ETFE laminated pistons produced with (Inv. Sample D) andwithout (Comp. Sample 5) release liners using helium leak testing. Thehelium leak rate is an industry standard used to quantify the quality ofa seal, using helium as an inert tracer gas. Though the same improvedsurface finish can be imparted to bare rubber articles through anomission of one film layer, CCI is not impacted by the change in surfaceroughness, likely because its viscoelastic flow fills surface defectsunder pressure. When the finished article is laminated by a polymerfilm, the film cannot flow and any surface imperfections (on eithersealing surface) create a leakage path. FIGS. 14-16 illustrates thefinal roughness of the sealing surface is critical to performance andinitial roughness of the film does not necessarily correlate to thefunctional performance under all circumstances. The threshold value of6×10⁻⁶ atm*cc/sec for sterility comes from the articles by Kirsch, et.al., titled “Pharmaceutical container/closure integrity,” which isconsistent with USP 1207. Although PTFE and ETFE were laminated pistonswere produced for these experiments, one having ordinary skill wouldreadily appreciate that other laminates would improve sealingperformance of a rubber elastomer using a release liner.

FIGS. 17 and 18 illustrate the performance of PTFE laminated pistonsproduced with a release liner. Specifically, FIG. 17 illustrates theBreak Loose Force and Average Extension Force for Inv. Sample C inCrystal Zenith® polymer, Silicone-Free Glass, and Baked-On SiliconeGlass under dry conditions using an Instron BLE method at 304.8 mm/min.FIG. 18 illustrates the Break Loose Force for Sample C in CrystalZenith® polymer, Silicone-Free Glass, and Baked-On Silicone Glass underdry and wet conditions using an Instron BLE method at 304.8 mm/min (notetests were not conducted for Sample C in Baked-On Silicone Glass underwet conditions). As with the marked improvement in the sealingperformance, PTFE laminated pistons produced with a release liner havesimilar Break Loose Force and Average Extension Force characteristics assome commercially available pistons that require the use of silicone oil(although commercially available pistons used with silicone oil were nottested in this experiment). The improved force performance is due to theentire contacting surfaces of the piston (i.e., the sidewall and crownsurfaces) being coated with a lubricious inert film rather than only thedrug interface surface as is typically done (if at all) for pistonsintended to be used with silicone oil. Although this experiment onlycharacterized the force performance of PTFE laminated pistons, onehaving ordinary skill in the art would appreciate that ETFE and otherlaminated pistons produced with a release liner would also have improvedforce characteristics in various barrel configurations.

The present method could also be used to make an elastomeric articlewithout any laminated film layer (i.e., bare elastomer protected duringmolding process by release film layer 46). Other surface modificationsmay include chemical functionalization, coatings requiring a smoothsubstrate.

A superior control of surface roughness may enable tunability of totalcontact area, and therefore improve other functional attributes (i.e.,break loose and extrusion forces). Similarly, this may enable productgeometries not previously possible.

This product could similarly be prepared through the design of newmolds. Other possible production methods include, but are not limitedto, polished molds, molds without sharp features (to avoid film damage),PTFE (or other polymer) coated molds, alternate mold materials (i.e.polymer or ceramic), alternate mold-release technologies. However, dueto the how the release film layer protects the inert film layer fromsurface features of the mold, the invention lends itself well to roughmolds and may extend the service life of any mold—ultimately reducingcosts.

The invention could be advantageously used in any type of seal used tocontain or contact injectable drugs. This includes, but is not limitedto pistons, stoppers, and lined seals. The greatest need for theinvention is in silicone-free containment systems for injectablemedicines, because CCI is critical to maintain in these systems. Theinvention is more advantageously used for sensitive biologic drugs andintraocularly deliverable drugs. The invention could also beadvantageously used to reduce manufacturing costs for any elastomer forcontainment of injectable medicine which has good barrier properties.

The inventive technology could be used for production of fully orpartially-film laminated pistons, stoppers, etc., and/or silicone-freeclosure systems with barrier properties. Preferably, the inventivetechnology is used for production of fully-film laminated pistons,stoppers, etc., and/or silicone-free closure systems with barrierproperties.

Certain terminology is used in the following description for convenienceonly and is not limiting. The words “proximal,” “distal,” “upward,”“downward,” “bottom,” and “top” designate directions in the drawings towhich reference is made. The words “inwardly” and “outwardly” refer todirections toward and away from, respectively, a geometric center of thedevice, and designated parts thereof, in accordance with the presentinvention. Unless specifically set forth herein, the terms “a,” “an,”and “the” are not limited to one element, but instead should be read asmeaning “at least one.” The terminology includes the words noted above,derivatives thereof and words of similar import.

It will be appreciated by those skilled in the art that changes could bemade to the embodiments described above without departing from the broadinventive concept thereof. It is understood, therefore, that thisinvention is not limited to the particular embodiments disclosed, but itis intended to cover modifications within the spirit and scope of thepresent invention.

1. A method for manufacturing at least one elastomeric articlecomprising the steps of: placing into a mold an assembly of an uncuredelastomeric sheet, a first film fully covering the elastomeric sheet anda second film covering the first film, such that the second film is incontact with and positioned between the first film and an interiorsurface of the mold; curing the assembly in the mold, such that thefirst film is laminated onto the elastomeric sheet thereby forming theat least one elastomeric article; and removing the second film from theelastomeric article.
 2. The method of claim 1, wherein prior to curingthe assembly, the first film placed into the mold has a surfaceroughness characterized by a peak density, and after removing the secondfilm, the peak density of the first film is increased.
 3. The method ofclaim 2, wherein the peak density of the first film is increased by atleast 3%.
 4. The method of claim 2, wherein the peak density of thefirst film is increased by at least 25%.
 5. The method of claim 2,wherein the peak density of the first film is increased by 3% to 165%.6. The method of claim 2, wherein the peak density of the first film isincreased by 25% to 35%.
 7. An elastomeric article for sealing acontainer comprising: an elastomeric body having an external sidewallsurface and an external crown surface; a first fluoropolymer film layerhaving an internal surface and an external surface, the internal surfaceof the first fluoropolymer film layer being laminated to an entirety ofthe external sidewall and crown surfaces of the elastomeric body, theexternal crown surface of the first fluoropolymer film layer including adrug contact surface configured to contact a drug contained in thecontainer and the external sidewall surface including a sealing surfaceconfigured to contact an interior surface of the container, wherein theexternal surface of the first fluoropolymer film layer is substantiallyfree of striations.
 8. The elastomeric article of claim 7, wherein thesealing surface has a surface roughness characterized by a peak densitygreater than 50,000 peaks/mm² when applying a Gaussian filter of 2.0microns or a peak density greater than 300,000 peaks/mm² when applying aGaussian filter of 0.08 microns.
 9. The elastomeric article of claim 7,wherein the sealing surface has a surface roughness characterized by apeak density greater than 100,000 peaks/mm² when applying a Gaussianfilter of 2.0 microns or a peak density greater than 500,000 peaks/mm²when applying a Gaussian filter of 0.08 microns.
 10. The elastomericarticle of claim 7, wherein the sealing surface has a surface roughnesscharacterized by a peak density greater than 150,000 peaks/mm² whenapplying a Gaussian filter of 2.0 microns or a peak density greater than600,000 peaks/mm² when applying a Gaussian filter of 0.08 microns. 11.The elastomeric article of claim 7, wherein the sealing surface has asurface roughness characterized by a peak density greater than 200,000peaks/mm² when applying a Gaussian filter of 2.0 microns or a peakdensity greater than 700,000 peaks/mm² when applying a Gaussian filterof 0.08 microns.
 12. The elastomeric article of claim 7, wherein theelastomeric article is a piston.
 13. The elastomeric article of claim 7,wherein the elastomeric article is a vial stopper.
 14. (canceled) 15.The elastomeric article of claim 7, wherein the external surface of thefirst fluoropolymer film has a mirror-like finish.
 16. A device forinjecting a drug, comprising: a silicone-free barrel; and an elastomericpiston having a laminated film layer in contact with the silicone-freebarrel, an interface between the laminated film layer and thesilicone-free barrel having a seal which withstands leakage of gas ofless than about 6×10⁻⁶ atm*cc/sec, wherein an external surface of thelaminated film layer is substantially free of striations.
 17. Theinjection device of claim 16, wherein actuation of the piston within thebarrel exerts a sliding force on the barrel less than 15 N.
 18. Theinjection device of claim 16, wherein actuation of the piston within thebarrel exerts a sliding force on the barrel less than 10 N.
 19. Theinjection device of claim 16, wherein actuation of the piston within thebarrel exerts a sliding force on the barrel less than 7.5 N.
 20. Theinjection device of claim 16, wherein actuation of the piston within thebarrel exerts a sliding force on the barrel less than 5 N.
 21. Theinjection device of claim 16, wherein the barrel is comprised of glass.22. The injection device of claim 16, wherein the barrel is comprised ofa polymer.
 23. The injection device of claim 16, wherein the laminatedfilm layer is comprised of a fluoropolymer.
 24. The injection device ofclaim 16, wherein the laminated film layer in contact with thesilicone-free barrel is a sealing surface having a surface roughnesscharacterized by a peak density greater than 50,000 peaks/mm² whenapplying a Gaussian filter of 2.0 microns or a peak density greater than300,000 peaks/mm² when applying a Gaussian filter of 0.08 microns. 25.The injection device of claim 16, wherein the laminated film layer incontact with the silicone-free barrel is a sealing surface having asurface roughness characterized by a peak density greater than 100,000peaks/mm² when applying a Gaussian filter of 2.0 microns or a peakdensity greater than 500,000 peaks/mm² when applying a Gaussian filterof 0.08 microns.
 26. The injection device of claim 16, wherein thelaminated film layer in contact with the silicone-free barrel is asealing surface having a surface roughness characterized by a peakdensity greater than 150,000 peaks/mm² when applying a Gaussian filterof 2.0 microns or a peak density greater than 600,000 peaks/mm² whenapplying a Gaussian filter of 0.08 microns.
 27. A method formanufacturing a syringe piston or vial stopper, the method comprisingthe steps of: placing an uncured elastomeric sheet and a first filmfully covering the elastomeric sheet into a mold; curing the elastomericsheet with the first film in the mold into a syringe piston or vialstopper; removing the syringe piston or vial stopper from the mold; andremoving the first film from the syringe piston or vial stopper.
 28. Themethod of claim 27, further comprising placing a second film into themold, the second film being positioned between the elastomeric sheet andthe first film.
 29. The method of claim 27, further comprising placing asecond film into the mold, the first film being positioned between theelastomeric sheet and the second film.
 30. (canceled)
 31. (canceled) 32.The method of claim 27, wherein the second film is comprised of afluoropolymer.
 33. The method of claim 27, wherein removing the firstfilm from the at least one elastomeric article uncovers a sealingsurface on the at least one elastomeric article, the sealing surfaceconfigured to contact a container along a mutual perimetercircumscribing the at least one elastomeric article, the sealing surfacehaving a surface roughness characterized by a peak density greater than50,000 peaks/mm² when applying a Gaussian filter of 2.0 microns or apeak density greater than 300,000 peaks/mm² when applying a Gaussianfilter of 0.08 microns.
 34. The method of claim 27, wherein removing thefirst film from the at least one elastomeric article uncovers a sealingsurface on the at least one elastomeric article, the sealing surfaceconfigured to contact a container along a mutual perimetercircumscribing the at least one elastomeric article, the sealing surfacehaving surface roughness characterized by a peak density greater than100,000 peaks/mm² when applying a Gaussian filter of 2.0 microns or apeak density greater than 500,000 peaks/mm² when applying a Gaussianfilter of 0.08 microns.
 35. The method of claim 27, wherein removing thefirst film from the at least one elastomeric article uncovers a sealingsurface on the at least one elastomeric article, the sealing surfaceconfigured to contact a container along a mutual perimetercircumscribing the at least one elastomeric article, the sealing surfacehaving a surface roughness characterized by a peak density greater than150,000 peaks/mm² when applying a Gaussian filter of 2.0 microns or apeak density greater than 600,000 peaks/mm² when applying a Gaussianfilter of 0.08 microns.
 36. The method of claim 27, wherein removing thefirst film from the at least one elastomeric article uncovers a sealingsurface on the at least one elastomeric article, the sealing surfaceconfigured to contact a container along a mutual perimetercircumscribing the at least one elastomeric article, the sealing surfacehaving a surface roughness characterized by a peak density greater than200,000 peaks/mm² when applying a Gaussian filter of 2.0 microns or apeak density greater than 700,000 peaks/mm² when applying a Gaussianfilter of 0.08 microns.